This research proposal is concerned with the role of virus M protein in influenza virus replication, its detailed structure and its relationship to the nonstructural (NS) component. A chromatographic procedure has been worked out whereby it will be possible to establish if any relationship exists between the controversial nonstructural component found in great abundance within the infected cell and the virus M protein, both of which have relatively similar molecular weights. This controversial protein has recently been found (unpublished observation of M. P. Morrongiello) as a constituent of large crystalline masses formed within the infected cell which come apart after isolation to resemble huge ribonucleoprotein-like structures. Analysis of this protein will be carried out to determine its identity and function in the replicagive process. Studies have been initiated to understand the basis for the biochemical defects of temperature-sensitive mutants of influenza virus available, none of which synthesize M protein. The possibility that these are structural mutants will be studied as will the role of the non-plaque former in contributing to the infective process. BIBLIOGRAPHIC REFERENCES: Gregoriades, A. and Hirst, G. K. (1975). The membrane protein of influenza virus and its distribution within the infected cell. In: Negative Strand Viruses, Vol. II (B. W. J. Mahy and R. D. Barry, eds.), Academic Press, New York, pp. 595-709. Gregoriades, A. and Hirst, G. K. (1976). Mechanism of influenza recombination. III. Biochemical studies of temperature-sensitive mutants belonging to different recombination groups. Virology 69, 81-92.